Cho, C. H.; Russett, C. S.; Harvey, Z. H.; Pende, N.; Hodgskiss, L. H.; Cangi, J.; Radler, P.; Hager, K.; Homola, M.; Imre, R.; Krssakova, G.; Ishii, S.; Ranawat, H. M.; Zink, I. A.; Maslac, N.; Hamm, J. N.; Spang, A.; Nobu, M. K.; Bulgheresi, S.; Dodonova, S. O.; Imachi, H.; Roitinger, E.; Irwin, N. A. T.; Schur, F. K. M.; Schleper, C.; Berger, F.

The emergence of the eukaryotes coincided with the diversification of histone proteins and their post-translational modifications by enzymes that constitute the core of eukaryotic chromatin. Yet the evolutionary origins of this regulatory machinery are unknown. Here, we show that the key molecular components of histone-based chromatin regulation are present in the Asgard archaea, the closest prokaryotic relatives of eukaryotes. Asgard histones are abundant and have extended N-terminal tails rich in lysine residues that can be post-translationally modified, all of which are features shared with eukaryotic histones. In line with these findings, we identify enzymes from Asgard archaea that deposit or remove lysine acetylation on histone tails in vitro. Moreover, Asgard sirtuin deacetylases (SIR2 proteins) restore chromatin silencing in yeast, demonstrating the functional compatibility of Asgard enzymes with eukaryotic histone substrates. Our findings establish that the foundations of histone-based chromatin predate eukaryogenesis and place Asgard archaea as an evolutionary intermediate in the emergence of eukaryotic chromatin.